This section is intended to provide a background or context to the invention disclosed below. The description herein may include concepts that could be pursued, but are not necessarily ones that have been previously conceived, implemented or described. Therefore, unless otherwise explicitly indicated herein, what is described in this section is not prior art to the description in this application and is not admitted to be prior art by inclusion in this section.
Microfluidic space devices offer benefits as they are in effect miniaturize laboratories with advantages of low-energy, low sample, and low by a receptor consumption; high integration, multiplexing, and compactness; fast results; and low cost. Moreover such devices have the potential for applications as research platforms as well as point-of-care devices.
Microfluidics also facilitates touchless manipulation of single cells, organisms, or particles through the exploitation of the “dielectrophoresis” effect. A dielectrophoretic (DEP) force arises from the polarization of otherwise electrically neutral particles or cells when suspended in a non-homogeneous electric field. This polarization occurs due to the imbalanced distribution of bounded charges induced by the electric field, and acts to attract (repel) cells to (from) electric field maxima for positive (negative) dielectrophoresis force, as described in the following equation:FDEP=2πR3εmCM  (1)
where                R: Radius        εm: permittivity        CM: Claussius-Mossotti Factor        
These forces depend not only on the geometrical configuration and excitation scheme of the electric field but also on the dielectric properties of the cell and of its suspending medium, hence can be used for particle discrimination, separation, isolation or concentration, useful for sample processing.
Particle or cell manipulation through dielectrophoresis requires creating an electric field gradient within the sample fluid, which prior to this invention could be done two different ways: (1) with an arrangement planar metallic electrodes integrated in the microfluidic channel, often in direct contact with the fluid containing the particles or cells; or (2) with highly focused laser beams commonly known as Optical Tweezers requiring large and expensive optical equipment.
Integrated electrodes in microfluidic channels can be used with other purposes in addition to generating DEP forces (both positive or negative) such as electrical sensing (impedance, capacitance, etc.), optical illumination and detection, heating mechanism to induce reactions, etc.
Common materials used as metallic electrodes, such as aluminum (Al), gold (Au), platinum (Pt), palladium (Pd), are used in part due to their stability when used in direct contact with the flow at moderate electrical voltages. Integration of metallic electrodes into microfluidic channels is most commonly done on silicon substrates, but it has also been used on glass substrates. They may also be used in plastic substrates. Common thickness of these metallic electrodes is of the order of 50 nm-100 nm. Occasionally a thin (˜5 nm) layer of titanium (Ti) is deposited between substrate and electrode to improve adhesion. The topography created by the electrodes on the path of the fluid can interfere with the progression of the flow meniscus, for instance, during filling of the channel, or with the particles suspended in the fluid, causing them to stick to the surface, especially with cells or other biological organisms. Thus, fabrication techniques have been devised to minimize the topography introduced by the integrated electrodes Ex: including one additional etching step to undercut into the substrate surface (ex: silicon oxide) prior to metal deposition. (See: WO 2014/207618 A1 “Microfluidic chip with dielectrophoretic electrodes extending in hydrophilic flow path) This can add complexity to the manufacturing process that needs to be well calibrated to etch a precise depth.
In addition, metallic structures can also impact cell integrity, react with the sample and cause bubbles due to electrolysis at high electric fields. Further challenges with metallic electrodes arise when employing optical detection methods where opaque metallic electrodes can interfere with the image. In addition, metallic electrodes are not flexible to be used on flexible substrates such as polymers, plastic, paper, and are harder to dispose (due to cost, contamination concerns) when used on low cost and disposable substrates.
On the other hand, certain inorganic layered materials (e.g. graphene, MoS2, WSe2, black phosphorus), regular arrays and random networks/thin films made of quasi-one dimensional lattice structures such as organic and inorganic nanotubes/nanowires (e.g. carbon nanotubes, Si nanowires, . . . ) can be used for implementation of similar functionalities as described above for metallic electrodes. Moreover, some are 2D semiconducting materials with the added functionality for gate modulated processes such light emission and detection. In addition, a process exists (see YOR820140381: Microfluidic and nanofluidic chips with application-specific device arrays employing a two-dimensional lattice structure) for transferring a 2-dimensional lattice structure onto a substrate patterned with microchannel topography, and for patterning the 2-dimensional lattice structure afterwards into arbitrary shapes within the microfluidic device.
Transfer is achieved by growing or depositing a 2-dimensional material (e.g. graphene or a carbon nanotube film) on a substrate and to spin-on a layer of e.g. PMMA for transfer (or by dissolving the substrate itself). The 2D material plus PMMA layer system is then deposited on top of the channel system before the PMMA is removed in a final lift-off step. Subsequent patterning of the 2-dimensional lattice is achieved through standard semiconductor fabrication methods. Additional patterning and contacting steps can follow before the final capping or sealing of the channel.
The current invention moves beyond these techniques and materials.
Abbreviations that may be found in the specification and/or the drawing figures are defined below, after the detailed description section.